Identification of a novel and myeloid specific role of the leukemia-associated fusion protein DEK-NUP214 leading to increased protein synthesis
Identification of a novel and myeloid specific role of the leukemia-associated fusion protein DEK-NUP214 leading to increased protein synthesis
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DOI：
10.1002/gcc.20531
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发表时间：
2008-04-01
影响因子：
3.7
通讯作者：
Lindmark, Anders
中科院分区：
文献类型：
--
作者：
Ageberg, Malin;Drott, Kristina;Lindmark, Anders
在部分急性髓系白血病(AML)患者中发现t(6；9)(p22；q34)染色体易位。易位导致核磷蛋白DEK和核孔蛋白NUP214(以前的CaN)之间的融合。融合蛋白DEK-NUP214促进白血病发生的机制尚未确定，以前也没有描述过DEK-NUP214对正常细胞功能的破坏。在本研究中，我们展示了DEK-NUP214融合蛋白的一种新的作用。我们的发现显示，在表达DEK-NUP214的细胞中，全球蛋白质合成显著增加。此外，我们得出的结论是，这种效应不是转录失调的结果，而仅仅是翻译增加的结果。与AML的关联一致，DEK-NUP214介导的蛋白质合成增加仅限于髓系细胞。对调节蛋白质合成的潜在机制的分析表明，DEK-NUP214的表达与翻译起始蛋白eIF4E的磷酸化有关。目前的数据提供了证据，翻译活性的增加构成了DEK-NUP124的致白血病作用可能通过其介导的机制。(C)2008年Wiley-Liss，Inc.
The t(6;9)(p22;q34) chromosomal translocation is found in a subset of patients with acute myeloid leukemia (AML). The translocation results in a fusion between the nuclear phosphoprotein DEK and the nucleoporin NUP214 (previously CAN). The mechanism by which the fusion protein DEK-NUP214 contributes to leukemia development has not been identified, and disruptions of normal cellular functions by DEK-NUP214 have previously not been described. In the present study, a novel effect of the DEK-NUP214 fusion protein is demonstrated. Our findings reveal a substantial increase in global protein synthesis in DEK-NUP214 expressing cells. Furthermore, we conclude that this effect is not the result of dysregulated transcription but merely due to increased translation. Consistent with the association with AML, the increased protein synthesis mediated by DEK-NUP214 is restricted to cells of the myeloid lineage. Analysis of potential mechanisms for regulating protein synthesis shows that expression of DEK-NUP214 correlates to the phosphorylation of the translation initiation protein, EIF4E. The present data provide evidence that increase of translational activity constitutes a mechanism by which the leukemogenic effect of DEK-NUP124 may be mediated. (C) 2008 Wiley-Liss, Inc.